WO2019140433A1 - Composition et procédé pour la libération contrôlée d'acides aminés - Google Patents

Composition et procédé pour la libération contrôlée d'acides aminés Download PDF

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Publication number
WO2019140433A1
WO2019140433A1 PCT/US2019/013612 US2019013612W WO2019140433A1 WO 2019140433 A1 WO2019140433 A1 WO 2019140433A1 US 2019013612 W US2019013612 W US 2019013612W WO 2019140433 A1 WO2019140433 A1 WO 2019140433A1
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amino acid
leucine
polysaccharide
soluble
soluble polysaccharide
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PCT/US2019/013612
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English (en)
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Gaurav Parekh
Brent Petersen
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Glanbia Nutritionals (Ireland), Ltd.
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Priority to JP2020560114A priority Critical patent/JP2021511071A/ja
Publication of WO2019140433A1 publication Critical patent/WO2019140433A1/fr

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/231Pectin; Derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/25Exudates, e.g. gum arabic, gum acacia, gum karaya or tragacanth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention relates to amino acid compositions which provide amino acids in more bioavailable forms. More specifically, the invention relates to compositions which provide improved delivery of non- polar amino acids for absorption in a human and/or animal body, and methods for making those compositions.
  • Leucine is a branched-chain amino acid, and an essential amino acid. It is the only amino acid that is converted to acetyl-coenzyme A and alpha-keto acids, and is an important source of nitrogen for synthesis of glutamine. In addition to its effects on protein synthesis and degradation, leucine also stimulates glucose uptake by protein kinase C (PKC), while insulin modulates glucose uptake via protein kinase B.
  • PKC protein kinase C
  • Whey proteins are a good source of leucine, but for many individuals who need the muscle-building amino acids dietary proteins can provide, it can be difficult to digest and/or absorb proteins. Furthermore, even for individuals who have normal digestion/absorption, Leucine (L-Leucine), being a non-polar amino acid with low solubility in water (24.3 mg/ml, except at very acidic pH) presents delivery and bioavailability issues.
  • Leucine L-Leucine
  • leucine Because the solubility of leucine is pH-dependent, it tends to be released from pharmaceutical carriers or molecular complexes much more rapidly in the stomach (where the pH ranges from about 1 to 4.5 based on the type and volume of food eaten), but significantly more slowly in the small intestine (where the pH is about 6 in the duodenum and gradually increases to about 7.4 in the terminal ileum), where absorption into the bloodstream would actually take place. It is therefore important to find ways to provide leucine-containing amino acid
  • compositions that provide those amino acids in a more bioavailable form which would decrease the release rate in the stomach and increase it in the intestine.
  • Various methods have been used for delivery of leucine which, being a non-polar amino acid, presents some challenges when formulating compositions for efficient delivery. For example, one approach has been to disperse leucine in water at or near neutral pH .
  • Various encapsulating agents have also been used, including, for example, gum acacia in combination with at least one other agent such as sucrose fatty acid ester ⁇ i.e., sugar esters) and/or sodium carboxymethyl starch. Hydrolyzed whey protein has also been used to encapsulate L- leucine.
  • the recommended daily dosage of leucine is about 63 mg/kg body weight (http://www.cdc.gov/nchs/data/nhanes/databriefs /adultweight.pdf). For an average healthy male that should be about 4.032g /day. Delivery of effective amounts of leucine in bioavailable form can be particularly important for athletes, older individuals, and
  • the invention relates to a composition
  • a composition comprising a coacervate consisting essentially of one or more amino acids (i.e., at least one amino acid) and at least one soluble polysaccharide. While the composition may contain additional ingredients such as food ingredients, flavorings, vitamins, minerals, for example, the coacervate within the composition will consist essentially of at last one amino acid and at least one soluble polysaccharide.
  • the amino acid is non-polar.
  • the amino acid is L-leucine.
  • the at least one soluble polysaccharide is gum acacia.
  • the coacervate comprises from about 45 to about 50 percent amino acid, by weight of the coacervate.
  • a leucine/soluble polysaccharide coacervate of the invention for example, provides a modified-release leucine composition that provides increased leucine delivery to the human and/or animal intestine.
  • the invention also relates to a method for making a composition comprising an amino acid/soluble polysaccharide coacervate, the method comprising (a) dissolving at least one amino acid in water, adjusted to a pH of from about 1.0 to about 1.1, to produce an amino acid solution; (b) admixing at least one soluble polysaccharide with the amino acid solution, to produce an amino acid/polysaccharide admixture; and (c) adjusting the pH of the amino acid/polysaccharide admixture to from about 2.3 to about 2.5 to produce an amino acid/polysaccharide coacervate.
  • a powdered amino acid/soluble polysaccharide modified delivery composition can be formed by adding a step of (d) drying the amino acid/polysaccharide coacervate.
  • the at least one soluble polysaccharide is selected from the group consisting of gum acacia, pectin, soy-soluble polysaccharides, pea-soluble polysaccharides, and combinations thereof.
  • a method for making a composition comprising an amino acid/soluble polysaccharide coacervate comprises the steps of (a) dissolving at least one soluble polysaccharide in water which has been preheated to from about 110 to about 122 degrees Fahrenheit and adjusted to a pH of from about 1.0 to about 1.5, to produce a soluble polysaccharide solution; (b) admixing at least one amino acid into the soluble polysaccharide solution, to produce an amino acid/polysaccharide admixture; and (c) adjusting the pH of the amino acid/polysaccharide admixture to from about 2.4 to about 3.1 to produce an amino acid/polysaccharide coacervate.
  • the method further comprises a step of drying the amino acid/polysaccharide coacervate.
  • the at least one soluble polysaccharide is selected from the group consisting of gum acacia, pectin, soy-soluble polysaccharides, pea-soluble polysaccharides, and combinations thereof.
  • the at least one soluble polysaccharide is gum acacia.
  • the at least one amino acid is non-polar, in some embodiments the amino acid is selected from the group consisting of leucine, glycine, alanine, proline, valine, isoleucine, methionine, tryptophan, phenylalanine, and
  • amino acid is an L- form amino acid such as, for example, L-leucine.
  • Fig. 1 is a general schematic of the coacervation process, using leucine as an example, according to the method of the invention.
  • Fig. 2a is a graph of particle size of L-leucine
  • Fig . 2b is a graph of particle size of L-leucine coacervate made according to the method of the invention using L-leucine obtained from the same source.
  • Fig. 3a is a graph of the particle size of L-leucine
  • Fig. 3b is a graph of the particle size of L-leucine coacervate made according to the method of the invention using L-leucine obtained from the same source.
  • Fig. 4 is a graph of Zeta potential of: free leucine (at pH 1.0), coacervated leucine with 0.36g/100g of gum acacia (GA), and coacervated leucine with 6.67g/100g of gum acacia (GA), both at pH 2.3-
  • Fig. 5. is a comparison of the release profiles of leucine (D) and of leucine from a leucine/soluble polysaccharide coacervate ( ⁇ ), with leucine produced by Ajinomoto North America, Inc.
  • Fig. 6 is a comparison of the release profiles of leucine from a leucine/soluble polysaccharide coacervate, with leucine produced by two different manufacturers: Shinestar (o) and Ajinomoto North America, Inc. ( ⁇ ).
  • a coacervate such as those which have previously been formed using larger molecules such as polypeptides and/or proteins with soluble polysaccharides such as gum acacia (gum Arabic), can be formed using isolated amino acid
  • the amino acid comprises at least one non-polar amino acid such as, for example, leucine (which typically has a low solubility in water), to directly deliver leucine to the human and/or animal intestine, rather than by forming a coacervate of protein/polysaccharide and encapsulating leucine therein.
  • leucine which typically has a low solubility in water
  • polysaccharide such as, for example, gum acacia
  • the inventor has also developed a composition that provides controlled delivery of leucine, providing significantly more leucine release in the environment of the small intestine, where it can be absorbed into the bloodstream.
  • Release is used herein to mean the diffusion of the soluble form of a chemical into the surrounding medium, thus making it available for absorption.
  • the surrounding media can be, for example, fluids within the various cavities of the gastrointestinal tract (i.e., stomach, duodenum, and small intestine).
  • the soluble chemical can be one or more non-polar amino acids, such as leucine, glycine, alanine, proline, valine, isoleucine, methionine, tryptophan, phenylalanine, and/or combinations thereof.
  • coacervates provide higher levels of amino acids such as leucine in a more concentrated form.
  • Leucine generally releases very quickly in the stomach, but is released much more slowly in that environment after being coacervated. Upon reaching the higher-pH environment of the small intestine, the coacervate provides a significantly higher rate/level of release than would a typical leucine product, such as a conventional capsule containing isolated leucine.
  • the invention therefore provides a method for producing modified-release compositions comprising amino acids, such as non-polar amino acids exemplified by leucine.
  • Leucine will be referred to herein both specifically, such as in the examples, and as a general representative of the group of non-polar amino acids.
  • the method of the invention can be used to form coacervates of either polar or non-polar amino acids, or both, but the inventors have discovered that the efficiency of formation is higher when non-polar amino acids are used. Therefore, the non-polar amino acids are even more ideally suited for modified delivery
  • the invention therefore relates to a composition
  • a composition comprising at least one coacervate consisting essentially of one or more isolated amino acids and at least one soluble polysaccharide.
  • the amino acid is leucine.
  • the at least one soluble polysaccharide is gum acacia.
  • the coacervate comprises leucine at from about 45 to about 50 percent by weight of the coacervate.
  • a method for making a composition comprising an amino acid/soluble polysaccharide coacervate comprises the steps of (a) dissolving at least one soluble polysaccharide in water which has been preheated to from about 110 to about 122 degrees Fahrenheit and adjusted to a pH of from about 1.0 to about 1.5, to produce a soluble polysaccharide solution; (b) admixing at least one amino acid into the soluble polysaccharide solution, to produce an amino acid/polysaccharide admixture; and (c) adjusting the pH of the amino acid/polysaccharide admixture to from about 2.4 to about 3.1 to produce an amino acid/polysaccharide coacervate.
  • the method further comprises a step of drying the amino acid/polysaccharide coacervate.
  • the at least one soluble polysaccharide is selected from the group consisting of gum acacia, pectin, soy-soluble polysaccharides, pea-soluble polysaccharides, and combinations thereof.
  • the at least one soluble polysaccharide is gum acacia.
  • the at least one amino acid is non-polar, in some embodiments the amino acid is selected from the group consisting of leucine, glycine, alanine, proline, valine, isoleucine, methionine, tryptophan, phenylalanine, and
  • the invention also relates to a method for making a leucine coacervate composition, the method comprising (a) dissolving leucine in water, which has been adjusted to a pH of from about 1.0 to about 1.1, to produce a leucine solution; (b) admixing into the leucine solution at least one soluble polysaccharide selected from the group consisting of gum acacia, pectin, soy-soluble polysaccharides, pea-soluble polysaccharides, and combinations thereof, to produce a
  • the method can further comprise a step (d), drying the leucine/polysaccharide coacervate.
  • coacervates are spherical aggregates of colloidal droplets held together by electrostatic forces. According to Schmitt and Turgeon (Protein/polysaccharide complexes and coacervates in food systems, Advances in Colloid and Interface Science 167 (2011) 63-70), when proteins and polysaccharides form these complexes, they generally originate from electrostatic interactions between oppositely charged macromolecules. As they explain, the interaction between those macromolecules impacts coacervate formation, viscosity, etc.
  • leucine can decrease the cost of providing leucine because it eliminates the need for the leucine-protein and/or polypeptide complex in previously-described coacervates, and, very importantly, delivers the leucine in a controlled-release form that targets delivery primarily to the intestine, where it is absorbed for use in the body.
  • G Gum arabic
  • acacia tree obtained from the acacia tree (and therefore also referred to as "gum acacia"), is a branched polysaccharide with six carbohydrate moieties and one polypeptide moiety.
  • GA is a weak polyelectrolyte with carboxylic groups that give it negative charge above pH 2.0. It is soluble in water and has low viscosity.
  • the polypeptide fraction is predominantly hydroxy proline and serine and is covalently bound to the reducing end of the polysaccharide chains.
  • Gulao, et al (Complex coacervates obtained from peptide leucine and gum arabic: Formation and characterization interactions, Food Chemistry 194 (2016) 680-686) used a polypeptide to which leucine has been non-covalently bound and demonstrated that interactions between the polypeptide and GA could "produce insoluble precipitates, complexes, or coacervates, depending on the polysaccharide amount, pH, and salt concentration.”
  • Livney Livney, Y.D., Complexes and conjugates of biopolymers for delivery of bioactive ingredients via food, in Delivery and Controlled Release of Bioactives in Foods and Nutraceuticals, 2008, p.
  • [c]omplex formation occurs between biopolymers exhibiting attractive interactions, including mainly electrostatic attraction between oppositely charged fixed groups on the polymers.
  • attractive interactions including mainly electrostatic attraction between oppositely charged fixed groups on the polymers.
  • other attractive interactions may also play important roles, e.g. hydrogen bonds, Van der Waals and hydrophobic interactions.
  • compositions of the invention consist essentially of a first component consisting essentially of at least one amino acid, and a second component consisting essentially of at least one soluble
  • Soluble polysaccharides can be selected, for example, from the group consisting of pectin, maltodextrin, gum acacia (gum
  • soluble glucans such as, for example, b-glucans, chitosan sulfate, alginates, soy based soluble fiber, pea based soluble fiber, and
  • Gum acacia, soy soluble polysaccharide, and pea soluble polysaccharide are particularly effective for forming coacervates with amino acids, especially leucine, in the method of the invention.
  • leucine is solubilized in solution by adjusting the solvent (e.g., water) to a pH of from about 1.0 to about 1.1.
  • Soluble polysaccharide (SP) is added at a ratio of soluble polysaccharide to amino acid of from about 0.25 to about 0.6 amino acid/coacervating agent.
  • the solution is admixed to homogeneity (i.e., lumps of SP should not be noticeable in the solution) and the pH is adjusted to from about 2.3 to about 2.5.
  • the low solubility amino acid e.g., leucine
  • the percentage of amino acid (leucine) remaining in the coacervate with the SP will generally be from about 40 to about 65 percent (dry weight). At this point, the solutions will generally have a solids content of from about 8 to about 25, and even more preferably, from about 8.3 to about 24.9 percent.
  • the leucine/SP coacervate can be spray-dried, for example.
  • Suitable conditions for spray-drying include an inlet temperature of from about 392°F to about 464°F (200-240°C) and an outlet temperature of from about 194°F to about 212°F (90-100°C).
  • leucine is present in the coacervate powder at from about 45 to about 50% by weight, the recommended dosage would be about from about 126 to about 140 mg of leucine coacervate per kg body weight (8.06-8.96 g per day for an average-size adult, for example).
  • Leucine is readily available from a variety of commercial sources, as are the variety of soluble polysaccharides that can be used to produce leucine coacervates according to the method of the invention.
  • Compositions of the invention can be used in a variety of applications, such as powdered nutritional supplements, either alone or in combination with other nutritional ingredients, drink mixes, etc., or they may be used as ingredients in food and/or drink products.
  • leucine coacervates of the invention can be especially beneficial in products produced for athletes, with the significant amounts of leucine provided being used to build and repair muscle impacted by the effects of strenuous exercise.
  • Leucine coacervates of the invention can also be incorporated into powdered nutritional supplements, protein bars, snack foods, and drink formulations, such as nutritional shakes, puddings, etc., to benefit elderly individuals who are at risk for muscle wasting, which can negatively impact overall health, decrease mobility, lead to balance issues, as well as other physical issues which can not only lead to illness, but also to injury. They can also be administered in the form of tablets, capsules and gummies, which are quite common types of solid dosage forms currently used in the nutraceutical market.
  • Coacervate compositions of the invention can also be dual-benefit compositions that provide the benefits of the one or more amino acids, as well as the benefits associated with the soluble
  • soluble polysaccharide Many soluble polysaccharides are commonly referred to as “soluble fiber,” and the benefits of soluble fiber are well-known.
  • Certain soluble polysaccharides such as b-glucans, for example, have well-documented benefits such as improving cholesterol levels and heart health, inhibiting tumor growth, reducing tumor proliferation, and preventing tumor metastasis. These polysaccharides have been shown to boost the immune response, and they have been used in therapeutic regimens as an adjuvant to cancer chemotherapy and radiotherapy.
  • increasing the amount of protein in a meal and by providing additional leucine has been found to stimulate muscle protein synthesis.
  • muscle protein synthesis can be stimulated by meals with specific dietary proteins and specific combinations of dietary essential amino acids, particularly leucine, so for these individuals, leucine coacervates of the present invention may be especially beneficial.
  • Coacervates formed from leucine-containing peptides, or leucine-containing peptides to which leucine has non-covalently been bound have been shown to be of larger particle size than the size of the starting material (Gulao, et al (Complex coacervates obtained from peptide leucine and gum arabic: Formation and characterization interactions, Food Chemistry 194 (2016) 680-686), whereas coacervates of the present invention are of smaller particle size than the starting material. Since particle size can influence solubility, clarity of solutions into which the particles are solubilized, etc., leucine coacervates can also provide a greater variety of options for products into which formulators may want to incorporate supplemental leucine.
  • SP/s was dispersed (1.8-6.3g/100g) into heated, acidified water (pH 1.0-1.5; 110-122F ( ⁇ 43-50°C)), and then leucine was slowly added to this solution under continuous stirring to create a dispersion. The pH of the dispersion was then adjusted to 2.4-3.1 by the addition of base.
  • Incorporation efficiency of leucine in the coacervate was calculated by dispersing the leucine/SP powder in RO water, lOOg/L. The mixture was centrifuged to separate the non-dissolved leucine in the residue from the dissolved leucine in the supernatant. The residue was again dissolved in same volume of fresh RO water. Both the supernatant and the residue were analyzed for leucine content using UPLC-UV (ultra- performance liquid chromatography with UV detection). Incorporation Efficiency (%) was measured as the ratio between the amount (g/lOOg) of leucine in the supernatant plus residue, divided by the weight of powder taken for the dissolution study (g/lOOg). The % incorporation after the spray-drying process was calculated to be 46%.
  • 1 mL release medium was dispersed in 20mL PBS (0.3M) buffer. The pH was maintained at approximately 1.0. Release was assessed under continuous stirring. At various time points (0, 15 min., 30 min., 1 hr., 2 hr.), 1 mL of dispersion was taken out and washed at 13000 rpm for 5 min, and the same volume (lmL) of fresh PBS buffer (of same pH) was added to the dispersion. The supernatant was subjected to UPLC. The residue was dispersed in lmL of fresh PBS buffer and vortexed. If any particles were seen floating in the tube, 1-2 drop of 6N HCI was added to it, then vortexed.
  • This residue sample was also subjected to UPLC.
  • the pH of the dispersion was then changed to 4.5, the sampling steps were repeated at time points 0, 15 min., 30 min., 1.5 hr.
  • the pH of the dispersion was then changed to 6.8, repeating the sampling steps again at 0, 15 min., 30 min., 1 hr., and 2 hr.
  • the release profile of leucine from the leucine/GA coacervate was about 60-65% within 2 hours at pH 1.0. At pH 4.5 there was a slow release of about 7-12% at pH 4.5.
  • Particle size was measured in microns, demonstrating that after the coacervate-forming process the leucine/gum arabic coacervate powder is 10 times smaller, with a narrower particle size distribution.
  • NanoBrook ZetaPlus Zeta Plus instrument from Brookhaven Instruments.
  • the uncoated leucine had a positive charge.
  • concentrations (1.8-6.3 g/lOOg) of SP were used, there was a reversal of surface charge having a negative zeta potential value of -13 to -17 mV, indicating that SP is coated on the leucine core.

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Abstract

L'invention concerne un coacervat de polysaccharide soluble dans l'acide aminé qui fournit une libération modifiée d'acide aminé dans le système digestif. L'invention concerne également un procédé de formation de compositions de coacervat d'acides aminés pour fournir une administration et une libération accrues d'un ou de plusieurs acides aminés, tels que la leucine, par exemple, dans l'intestin d'un être humain et/ou d'un animal.
PCT/US2019/013612 2018-01-15 2019-01-15 Composition et procédé pour la libération contrôlée d'acides aminés WO2019140433A1 (fr)

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